Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size

Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size

Sclerostin has emerged as an important regulator of bone mass. We have shown that sclerostin can act by targeting late osteoblasts/osteocytes to inhibit bone mineralization and to upregulate osteocyte expression of catabolic factors, resulting in osteocytic osteolysis. Here we sought to examine the...

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Main Authors: Kogawa, M, Khalid, Kamarul Ariffin, Wijenayaka, Asiri R, Ormsby, Renee T, Evdokiou, A, Anderson, Peter H, Findlay, David M, Atkins, Gerald J
Format: Article
Language:English
English
Published: 2018
Subjects:
QH301 Biology
QP Physiology
RD701 Orthopedics
Online Access:http://irep.iium.edu.my/69488/
http://irep.iium.edu.my/69488/1/ajpcell.00175.2017.pdf
http://irep.iium.edu.my/69488/7/Scopus%20-%20Document%20details.pdf
id iium-69488
recordtype eprints
spelling iium-694882019-01-24T11:24:32Z http://irep.iium.edu.my/69488/ Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size Kogawa, M Khalid, Kamarul Ariffin Wijenayaka, Asiri R Ormsby, Renee T Evdokiou, A Anderson, Peter H Findlay, David M Atkins, Gerald J QH301 Biology QP Physiology RD701 Orthopedics Sclerostin has emerged as an important regulator of bone mass. We have shown that sclerostin can act by targeting late osteoblasts/osteocytes to inhibit bone mineralization and to upregulate osteocyte expression of catabolic factors, resulting in osteocytic osteolysis. Here we sought to examine the effect of exogenous sclerostin on osteocytes in trabecular bone mechanically loaded ex vivo. Bovine trabecular bone cores, with bone marrow removed, were inserted into individual chambers and subjected to daily episodes of dynamic loading. Cores were perfused with either osteogenic media alone or media containing human recombinant sclerostin (rhSCL) (50 ng/ml). Loaded control bone increased in apparent stiffness over time compared with unloaded bone, and this was abrogated in the presence of rhSCL. Loaded bone showed an increase in calcein uptake as a surrogate of mineral accretion, compared with unloaded bone, in which this was substantially inhibited by rhSCL treatment. Sclerostin treatment induced a significant increase in the ionized calcium concentration in the perfusate and the release of -CTX at several time points, an increased mean osteocyte lacunar size, indicative of osteocytic osteolysis, and the expression of catabolism-related genes. Human primary osteocyte-like cultures treated with rhSCL also released -CTX from their matrix. These results suggest that osteocytes contribute directly to bone mineral accretion, and to the mechanical properties of bone. Moreover, it appears that sclerostin, acting on osteocytes, can negate this effect by modulating the dimensions of the lacunocanalicular porosity and the composition of the periosteocyte matrix. 2018 Article PeerReviewed application/pdf en http://irep.iium.edu.my/69488/1/ajpcell.00175.2017.pdf application/pdf en http://irep.iium.edu.my/69488/7/Scopus%20-%20Document%20details.pdf Kogawa, M and Khalid, Kamarul Ariffin and Wijenayaka, Asiri R and Ormsby, Renee T and Evdokiou, A and Anderson, Peter H and Findlay, David M and Atkins, Gerald J (2018) Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size. American Journal Of Physiology - Cell Physiology. ISSN 0363-6143 E-ISSN 1522-1563
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
English
topic QH301 Biology
QP Physiology
RD701 Orthopedics
spellingShingle QH301 Biology
QP Physiology
RD701 Orthopedics
Kogawa, M
Khalid, Kamarul Ariffin
Wijenayaka, Asiri R
Ormsby, Renee T
Evdokiou, A
Anderson, Peter H
Findlay, David M
Atkins, Gerald J
Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
description Sclerostin has emerged as an important regulator of bone mass. We have shown that sclerostin can act by targeting late osteoblasts/osteocytes to inhibit bone mineralization and to upregulate osteocyte expression of catabolic factors, resulting in osteocytic osteolysis. Here we sought to examine the effect of exogenous sclerostin on osteocytes in trabecular bone mechanically loaded ex vivo. Bovine trabecular bone cores, with bone marrow removed, were inserted into individual chambers and subjected to daily episodes of dynamic loading. Cores were perfused with either osteogenic media alone or media containing human recombinant sclerostin (rhSCL) (50 ng/ml). Loaded control bone increased in apparent stiffness over time compared with unloaded bone, and this was abrogated in the presence of rhSCL. Loaded bone showed an increase in calcein uptake as a surrogate of mineral accretion, compared with unloaded bone, in which this was substantially inhibited by rhSCL treatment. Sclerostin treatment induced a significant increase in the ionized calcium concentration in the perfusate and the release of -CTX at several time points, an increased mean osteocyte lacunar size, indicative of osteocytic osteolysis, and the expression of catabolism-related genes. Human primary osteocyte-like cultures treated with rhSCL also released -CTX from their matrix. These results suggest that osteocytes contribute directly to bone mineral accretion, and to the mechanical properties of bone. Moreover, it appears that sclerostin, acting on osteocytes, can negate this effect by modulating the dimensions of the lacunocanalicular porosity and the composition of the periosteocyte matrix.
format Article
author Kogawa, M
Khalid, Kamarul Ariffin
Wijenayaka, Asiri R
Ormsby, Renee T
Evdokiou, A
Anderson, Peter H
Findlay, David M
Atkins, Gerald J
author_facet Kogawa, M
Khalid, Kamarul Ariffin
Wijenayaka, Asiri R
Ormsby, Renee T
Evdokiou, A
Anderson, Peter H
Findlay, David M
Atkins, Gerald J
author_sort Kogawa, M
title Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
title_short Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
title_full Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
title_fullStr Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
title_full_unstemmed Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
title_sort recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size
publishDate 2018
url http://irep.iium.edu.my/69488/
http://irep.iium.edu.my/69488/1/ajpcell.00175.2017.pdf
http://irep.iium.edu.my/69488/7/Scopus%20-%20Document%20details.pdf
first_indexed 2023-09-18T21:38:39Z
last_indexed 2023-09-18T21:38:39Z
_version_ 1777412990864195584

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